Reirradiation and Concomitant Metronomic Temozolomide: An Efficient Combination for Local Control in Medulloblastoma Disease?

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Abstract

Medulloblastoma (MB) is the most common malignant pediatric brain tumor and a rare adulthood tumor. Twenty percent to 30% of patients relapses and displays a poor prognosis. The management of recurrent disease represents a medical challenge as salvage therapy with high-dose chemotherapy is disappointing. We report a pilot study of reirradiation and concomitant metronomic temozolomide of MB focal recurrence. Five patients from 10 to 27 years old at time of first diagnosis were treated initially with upfront radiation therapy at full dose. They relapsed focally and progressed under chemotherapy with a time recurrence ranged from 2 to 15 years after initial diagnosis. Patients were then treated with 3-dimensional conformal reirradiation focused on the relapsed disease with a median dose of 28 Gy (1.8 Gy per fraction) and concomitant temozolomide (75 mg/m2/d) alone or as part of a multidrug metronomic regimen. Five complete responses were obtained at the end of metronomic radiochemotherapy. The median follow-up was 28 months. At last follow-up, 3 patients progressed outside radiation field under maintenance chemotherapy, and 1 is free of disease. Only 1 patient relapsed in the reirradiation field. No neurological toxicity was observed. These results indicate a possible radiosensitizing effect of concomitant metronomic temozolomide with radiation therapy. This association could play a role in the management of high-risk MB patient with oligometastasis disease to increase local control.

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